TRPV1 channels facilitate glutamate transmission in the striatum.
Transient receptor potential vanilloid 1 (TRPV1) channels participate in the modulation of synaptic transmission in the periphery and in central structures. Here, we investigated the role of TRPV1 channels in the control of both excitatory and inhibitory transmission in the striatum. Pharmacological stimulation of TRPV1 channels with capsaicin (10 nM) selectively enhanced the frequency of glutamate-mediated spontaneous (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs) recorded from putative striatal medium spiny neurons. Capsaicin-mediated response underwent a rapid rundown, and was no longer detected in the majority of the neurons when the concentration of the drug was in the micromolar range, possibly due to receptor desensitization. Consistently, the totality of striatal neurons responded to capsaicin (10 nM or 10 microM) after prevention of desensitization of TRPV1 channels with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA). PMA was able per se to increase sEPSC frequency. The effects of capsaicin and of PMA were absent after pharmacological or genetic inactivation of TRPV1 channels. Finally, we provided evidence for anandamide as an endovanilloid substance in the striatum, since genetic inhibition of anandamide degradation resulted in a tonic activation of TRPV1 channels modulating glutamate but not GABA release. TRPV1-mediated regulation of excitatory transmission in the striatum might be important for the final output to other basal ganglia structures, and might play a role in several physiological and pathological processes.
Musella
Alessandra
A
Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
De Chiara
Valentina
V
Rossi
Silvia
S
Prosperetti
Chiara
C
Bernardi
Giorgio
G
Maccarrone
Mauro
M
Centonze
Diego
D
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D063388:Endocannabinoids; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011493:Protein Kinase C; C071423:capsazepine; D013755:Tetradecanoylphorbol Acetate; D002211:Capsaicin; C078814:anandamide